Objective: Molecular screening for frequently mutated genes may increase the likelihood of identifying cancer risk groups, such as patients with longstanding inflammatory bowel disease. This study investigated the prevalence and time course of p53 and K-ras mutations in colonic lavage fluid of patients with inflammatory bowel disease.

Methods: Colonic lavage fluid from 190 patients with ulcerative colitis (73), Crohn's disease (58) or controls (49 non-tumour, 10 colorectal cancer) was studied by oligomer-specific hybridization for K-ras mutations and single-strand conformation polymorphism (SSCP) for p53 mutations. Follow-up investigations were carried out after 1-3 years.

Results: Mutations were most frequent in carcinomas (5/10, 50%) and rare in non-tumour controls (1/49, 2.0%). They were found in Crohn's colitis in 15.4%, in extensive ulcerative colitis in 18.6%, in left-sided ulcerative colitis in 13.3%, and in distal ulcerative colitis in 6.7% (P > 0.05). There was a positive association with disease duration (> or =11 years, P < 0.05). Follow-up investigations detected the same mutation in four patients and revealed new mutations in three patients.

Conclusions: In our large series of patients with inflammatory bowel disease, K-ras and p53 mutations could be detected with reasonable frequency and confirmed at follow-up in at least some patients. Our data encourage the use of molecular screening for the detection of malignant precursor lesions in at-risk patients.